J. Kevin Foskett
Professor, Dept of Physiology
Chair, Cell Biology and Physiology Program

Cell Biology and Physiology Program

Address

B39 Anatomy-Chemistry Bldg.
3620 Hamilton Walk
Philadelphia, PA 19104

Office tel.: 215 898-1354
Lab tel.: 215 898-0468
Fax: 215 573-6808
E-mail: foskett@mail.med.upenn.edu


EDUCATION

Duke University: BS (Zoology), 1974.

University of South Carolina: MS (Marine Biology), 1977.

University of California: PhD (Zoology/Physiology), 1981.

RESEARCH INTERESTS

• ion channels, calcium signaling, cystic fibrosis.

Key words: signal transduction, genetic disease, apoptosis, Alzheimer's Disease, endoplasmic reticulum, ion channel, calcium, cystic fibrosis, electrophysiology.

Search PubMed for articles

DESCRIPTION OF RESEARCH

Our laboratory is most broadly interested in the molecular biology and physiological mechanisms of ion transport and intracellular signaling, and the roles of these processes in disease. Specifically, we are working in two distinct research areas:

First, we study the molecular physiology of intracellular calcium (Ca2+) release ion channels, esp. the inositol trisphosphate receptor. Calcium release from intracellular storage compartments is a ubiquitous cell signaling mechanism that regulates processes as diverse as fertilization, gene transcription, secretion and learning and memory. The calcium signaling system is amazingly complex in both time and space. A major problem in understanding how this signaling system works is that the release channel is located inside cells. We have developed novel approaches to overcome this limitation. We employ a variety of biophysical, molecular and biochemical approaches to study the molecular physiology of the inositol trisphosphate receptor calcium channel, ranging from single molecule studies to optical imaging of calcium signals in individual cells. Our foci now include the role of the channel in programmed cell death and Alzheimer's Disease. In the future we plan to utilize animal models.

The second focus of the lab is the disease cystic fibrosis. CF is the most common lethal recessive genetic disease. It is caused by mutations in the gene product, named CFTR, which is a chloride ion channel that is expressed in the tissues affected in the disease, including lungs, pancreas, reproductive tract and intestines. Our particular focus now is on lung physiology. Here again, we employ a variety of biophysical, molecular, genetic and biochemical approaches. Our most recent focus is on the molecular physiology of airway submucosal glands. We hope that by understanding the molecular machinery involved in submucosal gland function, we can better understand the lung pathophysiology in CF.

The techniques we employ span the spectrum from biophysical to molecular, reflecting our approach as cell physiologists. Biochemical and molecular tools are used within the context of physiological measurement. Our goal is to understand how molecular behavior results in complex cell physiological processes, including those involved in signal transduction and epithelial and nerve cell functions. We employ:

• electrophysiology, including nuclear envelope patch clamping, two-electrode voltage clamp of oocytes and single channel recording from mammalian cells;
• confocal and ratiometric imaging microscopy of single living cells
• microinjection
• yeast 2-hybrid system
• expression studies
• molecular biology
• biochemistry.

RECENT PUBLICATIONS

White, C., C. Li, J. Yang, N.B. Petrenko, M. Madesh, C. B. Thompson and J.K. Foskett. 2005. The endoplasmic reticulum gateway to apoptosis by Bcl-XL modulation of the InsP3R. Nature Cell Biology 7:1021-1028.

Mak, D.-O.D., J.E. Pearson, K.P. Loong , S. Datta, M. Fernandez-Mongil and J.K. Foskett. 2007. Rapid ligand-regulated gating kinetics of single InsP3 receptor Ca2+ release channels. EMBO Reports 8:1044-1051.

Cheung, K.H., D. Shineman, M. Muller, C. Cardenas, L. Mei, J. Yang, T. Tomita, T. Iwatsubo, V. M.-Y. Lee and J. K. Foskett. 2008. Mechanism of Ca2+ disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating. Neuron 58: (in press).

Foskett, J.K., C. White, K. H. Cheung and D.-O.D. Mak. 2007. Inositol trisphosphate receptor Ca2+ release channels. Physiol. Rev. 87:593-658.

Dreses-Werringloer, U., J. -C. Lambert, V. Vingtdeux, H. Zhao, H. Vais, A. Siebert, A. Jain, J. Koppel, A. Rovelet-Lecrux, D. Hannequin, F. Pasquier, D. Galimberti, E. Scarpini, D. Mann, C. Lendon, P. Amouyel, P. Davies, J. K. Foskett, F. Campagne and P. Marambaud. 2008. A polymorphism in CALHM1 influences Ca2+ homeostasis, A levels, and Alzheimer's disease risk. Cell: (in press).

Lee, R. J., J. M. Harlow, M. P. Limberis, J. M. Wilson and J. K. Foskett. 2008. HCO3- secretion by murine nasal submucosal gland serous acinar cells during Ca2+-stimulated fluid secretion. J. Gen. Physiol. (in press).

Lab

Lab personnel:

Dr. Daniel Mak, PhD (Research Investigator)
Dr. King Ho Cheung, PhD (Postdoctoral Fellow)
Dr. Cesar Cardenas, PhD (Postdoctoral Fellos)
Dr. Zhongming Ma, PhD (Postdoctoral Fellow)
Robert Lee (CAMB Graduate Student)
Adam Siebert (CAMB Graduate Student)
Dustin Shilling, Neuroscience Graduate Student
Marioly Muller (Univ. of Chile Graduate Student)
Lijuan Mei (Research Specialist)
Horia Vais (Research Specialist)
Vivek Kanumuri (Summer Undergraduate Student)